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DSMP Example: DSMP for a Phase II multicenter study of an approved agent used for a new indication.
This DSMP also includes the use of a Data and Safety Monitoring Committee
(DSMB).
This is a risk-level III, multi-center investigation of an approved agent used for a new
indication in a pediatric population. (Note: The SAC may not REQUIRE a DSMB for a risk-level
III study. The information below provides an example of a DSMP which includes a DSMB.)
Assessment and Reporting of Adverse Events (AE).
Oversight for this study at CHRMC will be provided by the PI with delegation of
responsibilities to sub-investigators and designated study personnel. They will ensure all
entry criteria are met prior to the initiation of the protocol and all study procedures and
reporting of adverse events are performed according to the IRB and SAC-approved protocol.
An adverse event is any physical or clinical change experienced by the patient. This includes
the onset of new symptoms and the exacerbation of pre-existing conditions. All AEs must be
recorded in the patient's medical records and on the CRF. The severity of the AE will be
assessed; actions/outcomes (e.g., hospitalization, discontinuation of therapy, etc.) will
also be recorded for each AE. Patients with adverse events will be monitored with relevant
clinical assessments and laboratory tests as determined by an investigator. All adverse
events must be followed to satisfactory resolution or stabilization of the event(s).
Any actions taken and follow-up results must be recorded on the appropriate page of the CRF,
as well as in the patient's source documentation. Follow-up laboratory results should be
filed with the patient's source documentation.
All treatment and study procedure-related adverse events occurring at the site will be
reported by the investigator to the IRB and the SAC of the GCRC according to the CHRMC
IRB guidelines.
The following definitions will be used:
| Mild: |
Awareness of sign, symptom, or event, but easily tolerated |
| Moderate: |
Discomfort enough to cause interference with usual activity and may warrant investigation. |
| Severe: |
Incapacitating with inability to do usual activities or significantly affects clinical status, and warrants intervention |
| Life-threatening: |
Immediate risk of death. |
The onsite investigator must also assess the relationship of any adverse event to study
procedure, based on available information, using the following guidelines:
| 0 = Unlikely |
no temporal association, or the cause of the event has been identified, or the procedure cannot be implicated |
| 1 = Possibly |
temporal association, but other etiologies are likely the cause; however, involvement of the procedure cannot be excluded |
| 2 = Probably |
temporal association, or other etiologies are possible, but unlikely. |
Serious Adverse Events (SAEs).
All serious adverse events, whether or not deemed procedure-related or expected, must be
reported by the to the study-monitor within 24 hours (one working day) by telephone. A
written report must follow as soon as possible, which includes a full description of the
event and any sequelae. This includes serious events that occur any time after the inclusion
of the patient in the study until completion of the last visit.
A serious adverse event is any event that:
- Is fatal
- Is life threatening (life threatening is defined as the patient was at immediate risk of death from the AE as it occurred)
- Is significantly or permanently disabling
- Requires hospitalization, or prolongs hospitalization
- Is a congenital anomaly or birth defect
Important medical events that may not result in death, be life-threatening, or require
hospitalization may be considered serious adverse experiences when, upon appropriate
medical judgement, they may jeopardize the patient and may require medical or surgical
intervention to prevent one of the outcomes listed in the definition. Examples of such
medical events include allergic bronchospasm requiring intensive treatment in an emergency
department or home, blood dyscrasias or convulsions that do no result in hospitalization,
or the development of drug dependency or abuse. The death of any patient during the study,
regardless of the cause, must be reported within 24 hours by telephone, to the study monitor.
A full written report must follow as soon as possible. If an autopsy is performed, a copy
should be provided to the study monitor.
Reports of all serious adverse events, including deaths, must be communicated to the
appropriate Institutional Review Board or ethical review committee and/or reported in
accordance with local laws and regulations.
Serious adverse events (SAE's) will be monitored by the Data Monitoring Committee (DMC) in
real time throughout the trial. SAE's must be reported by the Onsite Investigator to the
Therapeutic Development Network Coordinating Center (TDNCC) within 24 hours of learning
of the event. All SAE's that are reported to the TDNCC will be reviewed by a blinded medical
monitor. At the same time, the SAE report will be sent via fax to the DMC chair and to Dr.
X, the Principal Investigator at the lead institution (X).
In addition to monitoring SAE's, the chair of the DMC will be given monthly summaries of
safety data. This will include unblinded adverse event listings from all study patients
that will be provided by the TDN Data Management Unit. The DMC may at any point decide
that unblinding is necessary and may temporarily stop the study for concerns of patient
safety.
An interim analysis for safety will be conducted after 24 study subjects have completed the
protocol. At the time of interim analysis, a comprehensive unblinded safety report will be
generated for all members of the DMC to review. The safety report will be prepared by select
unblinded members of the TDN Statistical Analysis Unit (SAU), and will include a summary of
adverse event rates by treatment group. The purpose of this review is to determine whether
or not the study should be terminated for reasons of subject safety. Since the data to be
accumulated addresses both study medication efficacy and standardization of NPD results
between different TDN study sites, the interim analysis will only address safety concerns
and not efficacy.
The DMC may recommend early termination of the study for reasons of patient safety based on
the interim review of this data. This information will be communicated directly from the DMC
to the lead investigator (Dr. X) and Medical Monitor (Drs. X,X,X) at the TDNCC.
If additional concerning systemic symptoms are identified by the DMC, interim unblinded review
of the data and the study medication treatment group can be conducted at the discretion of the
DMC at any time following consultation with the Medical Monitor and the lead investigator (Dr.
X).
The DMC will communicate with the site PI of all study sites holding IRB approval for this
study. The DMC will report the following:
- The nature of the review (including pertinent safety data).
- A brief description of any serious adverse events or concerns regarding systematic adverse events.
- Decisions of the DMC regarding the study.
The site PI will forward the DMC communications to the IRB and PSAC.
The chairman of the DMC will be X, MD, at the University of Arizona. Dr. X has reviewed and
approved the protocol, and will establish a DMC consisting of two CF-clinicians (one of whom
will be Dr. X).
The contact information for Dr. X is provided below:
Telephone:
Fax:
E-mail:
See Appendix 1 for the DMC charter.
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